Helicobacter pylori, originally named Campylobacter pylori, is a curved, microaerophilic, gram-negative bacterium that exhibits high urease and catalase activity. Recent studies suggest that H. pylori infection may be either a cause of, or a cofactor in, type B gastritis, peptic ulcers, and gastric tumors. See, e.g., Blaser, Gastroenterology (1987) 93:371-383; Dooley et al., New Eng. J. Med. (1989) 321:1562-1566; Personnet et al., New Eng. J. Med. (1991) 325:1127-1131. In this regard, H. pylori colonizes the human gastric mucosa and causes an infection that can persist for decades. Many people with this condition are asymptomatic but are nonetheless at a considerable risk of developing peptic ulcers and/or gastric adenocarcinomas. For a review of H. pylori and its role in gastric disease, see, Telford et al., Trends in Biotech. (1994) 12:420-426 and Blaser, M. J., Scientific American (February 1996):104-107.
H. pylori bacteria are divided into two groups, Type I and Type II, based on the presence or absence of specific proteins. In this regard, H. pylori produces several factors that function to establish and maintain infection. For example, both Type I and Type II bacteria include flagella that aid in mobility in the viscous mucus layer of the stomach. Both types of bacteria also produce ureases, presumably to neutralize the acid environment of the stomach. Additionally, the two types of bacteria produce a number of adhesins for tissue-specific colonization. On the other hand, only H. pylori Type I strains produce a potent cytotoxin, known as VacA or CT, as well as a surface-exposed immunodominant antigen which is associated with cytotoxin expression, known as CagA, CAI antigen or tagA. For descriptions of VacA and CagA, see, e.g., International Publication No. WO 93/18150, published 16 Sep. 1993.
Patients with duodenal ulcers have been shown to produce antibodies to VacA and CagA and antibody titers appear to correlate with the severity of the disease. For example, in one study, more than 95% of patients with duodenal ulcer or duodenitis, and more than 70% of patients suffering from gastric ulcer, were found to be CagA seropositive. Telford et al., Trends in Biotech. (1994) 12:420-426. Furthermore, a correlation has been shown between CagA serum response and gastric adenocarcinoma. Telford et al., supra. Additionally, only cytotoxic strains are able to induce gastric lesions in a laboratory animal model. See, e.g., Telford et al., J. Exp. Med. (1994) 179:1653-1658. Thus, it is believed that only individuals infected with H. pylori Type I strains develop severe disease.
Several assays have been developed for the diagnosis of H. pylori infection. These assays, unfortunately, suffer from several drawbacks. For example, bacterial culture assays have been described for the detection of H. pylori. U.S. Pat. No. 5,498,528 describes such a method for detecting H. pylori in saliva. The assay requires incubating the test sample with a culture medium that supports the selective growth of H. pylori. The presence of the bacterium is detected by the activity of the enzyme urease which, as described above, is produced by H. pylori. Urease catalyzes the conversion of urea to ammonium causing an increase in the pH of the culture medium. The pH change can be detected by a color change to the medium due to the presence of a pH sensitive indicator. However, the assay is time consuming since the bacteria require a number of days for growth. The assay is also inconvenient and bacterial samples may degrade or become contaminated during transport to the laboratory.
Antibody detection tests provide an alternative to bacterial culture. In this regard, subjects colonized with H. pylori mount a humoral immune response and produce antibodies to the bacterium that can be used as a basis for diagnosis. IgA antibodies are found in gastric fluid while IgG antibodies are found in the circulation. However, such tests can suffer from a lack of specificity since H. pylori appears to be antigenically cross-reactive with Campylobacter jejuni and C. coli. 
U.S. Pat. No. 4,882,271 describes an H. pylori assay that utilizes high molecular weight cell-associated proteins, on the order of 300 kDa to 700 kDa, having urease activity, in an enzyme-linked immunosorbent assay (ELISA), in an attempt to circumvent the problems with cross-reactivity.
International Publication No. WO 96/12965, published 2 May 1996, describes an immunoblot assay where a serological sample is reacted with two antigen components having molecular weights of 19.5 kDa, 26.5 kDa or 30 kDa, or alternatively, any one antigen component corresponding to a molecular weight of 35 kDa, 89 kDa, 116 kDa or 180 kDa. It is postulated by the inventors that the 19.5 kDa protein is a ferritin-like protein, the 26.5 and 30 kDa proteins are ureases, the 89 kDa protein is VacA, and that the 116 kDa protein is CagA. The 35 kDa and 180 kDa were uncharacterized.
Finally, European Patent Publication 329,570, published 23 Aug. 1989, describes immunoassays for H. pylori infection using pooled suspensions of sonicates of several H. pylori strains, as well as immunoassays using purified H. pylori flagellae.
Although faster and more sensitive than bacterial culture, antibody detection tests, such as those described above, can give false positive and negative results and generally do not distinguish between H. pylori Type I and Type II infection. Thus, an additional test must be conducted to determine whether the infection is due to H. pylori Type I or Type II.
Accordingly, the wide spread availability of an accurate and efficient assay for H. pylori infection that readily distinguishes between Type I and Type II infection, would be important for the diagnosis of infection in both symptomatic and asymptomatic individuals.